CA2376949C - Heterocyclic aminopyrrolidine derivatives as melatonergic agents - Google Patents

Heterocyclic aminopyrrolidine derivatives as melatonergic agents Download PDF

Info

Publication number: CA2376949C
Authority: CA; Canada
Prior art keywords: pyrrolidin; dihydrobenzofuran; urea; compound; alkyl
Prior art date: 1999-06-30
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

CA002376949A

Other languages

English (en)

French (fr)

Other versions

CA2376949A1 (en

Inventor

Katherine S. Takaki

Guanglin Luo

Stephen R. Bertenshaw

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-06-30

Filing date

2000-06-06

Publication date

2009-05-26

2000-06-06 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2001-01-11 Publication of CA2376949A1 publication Critical patent/CA2376949A1/en

2009-05-26 Application granted granted Critical

2009-05-26 Publication of CA2376949C publication Critical patent/CA2376949C/en

2020-06-06 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

-1 Heterocyclic aminopyrrolidine derivatives Chemical class 0.000 title abstract description 19
150000001875 compounds Chemical class 0.000 claims description 77
229910052739 hydrogen Inorganic materials 0.000 claims description 49
239000001257 hydrogen Substances 0.000 claims description 42
125000000217 alkyl group Chemical group 0.000 claims description 33
239000000203 mixture Substances 0.000 claims description 23
150000002367 halogens Chemical class 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 16
231100000252 nontoxic Toxicity 0.000 claims description 16
230000003000 nontoxic effect Effects 0.000 claims description 16
239000012453 solvate Substances 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
208000019116 sleep disease Diseases 0.000 claims description 10
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
230000027288 circadian rhythm Effects 0.000 claims description 7
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 6
230000001225 therapeutic effect Effects 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 5
239000004202 carbamide Substances 0.000 claims description 5
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 5
125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
YEWRWUULGQJYFI-SNVBAGLBSA-N 1-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-methylurea Chemical compound C1[C@H](NC(=O)NC)CCN1C1=CC=CC2=C1CCO2 YEWRWUULGQJYFI-SNVBAGLBSA-N 0.000 claims description 2
AWNSPIJVWCYCEZ-SECBINFHSA-N 1-[(3r)-1-(5,7-dichloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@H](NC(=O)NCC)CCN1C1=C(CCO2)C2=C(Cl)C=C1Cl AWNSPIJVWCYCEZ-SECBINFHSA-N 0.000 claims description 2
IVJGPMCIBXYTDK-SNVBAGLBSA-N 1-[(3r)-1-(5-chloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@H](NC(=O)NCC)CCN1C1=C(CCO2)C2=CC=C1Cl IVJGPMCIBXYTDK-SNVBAGLBSA-N 0.000 claims description 2
ZMZBXCIVLQHCHS-JTQLQIEISA-N 1-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]-3-methylurea Chemical compound C1[C@@H](NC(=O)NC)CCN1C1=CC=CC2=C1OCCO2 ZMZBXCIVLQHCHS-JTQLQIEISA-N 0.000 claims description 2
YMMRKYFVXURJCG-LBPRGKRZSA-N 1-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]-3-propylurea Chemical compound C1[C@@H](NC(=O)NCCC)CCN1C1=CC=CC2=C1OCCO2 YMMRKYFVXURJCG-LBPRGKRZSA-N 0.000 claims description 2
CDGKTTRAJGRLKP-NSHDSACASA-N 1-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@@H](NC(=O)NCC)CCN1C1=CC=CC2=C1CCO2 CDGKTTRAJGRLKP-NSHDSACASA-N 0.000 claims description 2
YEWRWUULGQJYFI-JTQLQIEISA-N 1-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-methylurea Chemical compound C1[C@@H](NC(=O)NC)CCN1C1=CC=CC2=C1CCO2 YEWRWUULGQJYFI-JTQLQIEISA-N 0.000 claims description 2
MGTDHASWIXDBRS-LBPRGKRZSA-N 1-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-propylurea Chemical compound C1[C@@H](NC(=O)NCCC)CCN1C1=CC=CC2=C1CCO2 MGTDHASWIXDBRS-LBPRGKRZSA-N 0.000 claims description 2
AWNSPIJVWCYCEZ-VIFPVBQESA-N 1-[(3s)-1-(5,7-dichloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@@H](NC(=O)NCC)CCN1C1=C(CCO2)C2=C(Cl)C=C1Cl AWNSPIJVWCYCEZ-VIFPVBQESA-N 0.000 claims description 2
IVJGPMCIBXYTDK-JTQLQIEISA-N 1-[(3s)-1-(5-chloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@@H](NC(=O)NCC)CCN1C1=C(CCO2)C2=CC=C1Cl IVJGPMCIBXYTDK-JTQLQIEISA-N 0.000 claims description 2
YYBSJXRHPDSHKX-GFCCVEGCSA-N 1-cyclopropyl-3-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]urea Chemical compound N([C@H]1CN(CC1)C=1C=2CCOC=2C=CC=1)C(=O)NC1CC1 YYBSJXRHPDSHKX-GFCCVEGCSA-N 0.000 claims description 2
MRHCVLSMVRDSOU-GFCCVEGCSA-N n-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-2-methylpropanamide Chemical compound C1[C@H](NC(=O)C(C)C)CCN1C1=CC=CC2=C1CCO2 MRHCVLSMVRDSOU-GFCCVEGCSA-N 0.000 claims description 2
FSSZVYLSEYZOSN-LLVKDONJSA-N n-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]acetamide Chemical compound C1[C@H](NC(=O)C)CCN1C1=CC=CC2=C1CCO2 FSSZVYLSEYZOSN-LLVKDONJSA-N 0.000 claims description 2
AUJCIORXQAONNC-GFCCVEGCSA-N n-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]butanamide Chemical compound C1[C@H](NC(=O)CCC)CCN1C1=CC=CC2=C1CCO2 AUJCIORXQAONNC-GFCCVEGCSA-N 0.000 claims description 2
MYPJFFALPYPMPA-GFCCVEGCSA-N n-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]cyclopropanecarboxamide Chemical compound N([C@H]1CN(CC1)C=1C=2CCOC=2C=CC=1)C(=O)C1CC1 MYPJFFALPYPMPA-GFCCVEGCSA-N 0.000 claims description 2
PZVPYLMOBPEFEF-LBPRGKRZSA-N n-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]butanamide Chemical compound C1[C@@H](NC(=O)CCC)CCN1C1=CC=CC2=C1OCCO2 PZVPYLMOBPEFEF-LBPRGKRZSA-N 0.000 claims description 2
SPJKCDNMZRORTE-LBPRGKRZSA-N n-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]cyclopropanecarboxamide Chemical compound N([C@@H]1CN(CC1)C=1C=2OCCOC=2C=CC=1)C(=O)C1CC1 SPJKCDNMZRORTE-LBPRGKRZSA-N 0.000 claims description 2
ZLXOEBIHHXQNOA-NSHDSACASA-N n-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]propanamide Chemical compound C1[C@@H](NC(=O)CC)CCN1C1=CC=CC2=C1OCCO2 ZLXOEBIHHXQNOA-NSHDSACASA-N 0.000 claims description 2
MRHCVLSMVRDSOU-LBPRGKRZSA-N n-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-2-methylpropanamide Chemical compound C1[C@@H](NC(=O)C(C)C)CCN1C1=CC=CC2=C1CCO2 MRHCVLSMVRDSOU-LBPRGKRZSA-N 0.000 claims description 2
FSSZVYLSEYZOSN-NSHDSACASA-N n-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCN1C1=CC=CC2=C1CCO2 FSSZVYLSEYZOSN-NSHDSACASA-N 0.000 claims description 2
MYPJFFALPYPMPA-LBPRGKRZSA-N n-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]cyclopropanecarboxamide Chemical compound N([C@@H]1CN(CC1)C=1C=2CCOC=2C=CC=1)C(=O)C1CC1 MYPJFFALPYPMPA-LBPRGKRZSA-N 0.000 claims description 2
UYVZRPXMIYGPKP-VIFPVBQESA-N n-[(3s)-1-(5,7-dichloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCN1C1=C(CCO2)C2=C(Cl)C=C1Cl UYVZRPXMIYGPKP-VIFPVBQESA-N 0.000 claims description 2
KRTWNLFWPIQTKL-JTQLQIEISA-N n-[(3s)-1-(5,7-dichloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]butanamide Chemical compound C1[C@@H](NC(=O)CCC)CCN1C1=C(CCO2)C2=C(Cl)C=C1Cl KRTWNLFWPIQTKL-JTQLQIEISA-N 0.000 claims description 2
ZUNCMYDGYGZFLH-JTQLQIEISA-N n-[(3s)-1-(5-chloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCN1C1=C(CCO2)C2=CC=C1Cl ZUNCMYDGYGZFLH-JTQLQIEISA-N 0.000 claims description 2
AKPPOVFZYRIAPL-NSHDSACASA-N n-[(3s)-1-(5-chloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]butanamide Chemical compound C1[C@@H](NC(=O)CCC)CCN1C1=C(CCO2)C2=CC=C1Cl AKPPOVFZYRIAPL-NSHDSACASA-N 0.000 claims description 2
QJQGMUCDDDACLE-NSHDSACASA-N n-[(3s)-1-(5-chloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]cyclopropanecarboxamide Chemical compound N([C@H]1CCN(C1)C1=C2CCOC2=CC=C1Cl)C(=O)C1CC1 QJQGMUCDDDACLE-NSHDSACASA-N 0.000 claims description 2
KZBMQAJAOUZADP-LBPRGKRZSA-N n-[[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]methoxy]acetamide Chemical compound C1[C@@H](CONC(=O)C)CCN1C1=CC=CC2=C1CCO2 KZBMQAJAOUZADP-LBPRGKRZSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 2
CDGKTTRAJGRLKP-LLVKDONJSA-N 1-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-ethylurea Chemical compound C1[C@H](NC(=O)NCC)CCN1C1=CC=CC2=C1CCO2 CDGKTTRAJGRLKP-LLVKDONJSA-N 0.000 claims 1
MGTDHASWIXDBRS-GFCCVEGCSA-N 1-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-3-propylurea Chemical compound C1[C@H](NC(=O)NCCC)CCN1C1=CC=CC2=C1CCO2 MGTDHASWIXDBRS-GFCCVEGCSA-N 0.000 claims 1
UFEOHLOXRSYLTE-LLVKDONJSA-N 3-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-1,1-dimethylurea Chemical compound C1[C@H](NC(=O)N(C)C)CCN1C1=CC=CC2=C1CCO2 UFEOHLOXRSYLTE-LLVKDONJSA-N 0.000 claims 1
UFEOHLOXRSYLTE-NSHDSACASA-N 3-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]-1,1-dimethylurea Chemical compound C1[C@@H](NC(=O)N(C)C)CCN1C1=CC=CC2=C1CCO2 UFEOHLOXRSYLTE-NSHDSACASA-N 0.000 claims 1
JNAKEKOTQGGNFU-LLVKDONJSA-N n-[(3r)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]propanamide Chemical compound C1[C@H](NC(=O)CC)CCN1C1=CC=CC2=C1CCO2 JNAKEKOTQGGNFU-LLVKDONJSA-N 0.000 claims 1
BIKBLOFIYHWTNQ-NSHDSACASA-N n-[(3s)-1-(2,3-dihydro-1,4-benzodioxin-5-yl)pyrrolidin-3-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCN1C1=CC=CC2=C1OCCO2 BIKBLOFIYHWTNQ-NSHDSACASA-N 0.000 claims 1
AUJCIORXQAONNC-LBPRGKRZSA-N n-[(3s)-1-(2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]butanamide Chemical compound C1[C@@H](NC(=O)CCC)CCN1C1=CC=CC2=C1CCO2 AUJCIORXQAONNC-LBPRGKRZSA-N 0.000 claims 1
JTLLOSNSQUXOSR-JTQLQIEISA-N n-[(3s)-1-(5,7-dichloro-2,3-dihydro-1-benzofuran-4-yl)pyrrolidin-3-yl]cyclopropanecarboxamide Chemical compound N([C@H]1CCN(C1)C1=C(Cl)C=C(C=2OCCC=21)Cl)C(=O)C1CC1 JTLLOSNSQUXOSR-JTQLQIEISA-N 0.000 claims 1
241000282414 Homo sapiens Species 0.000 abstract description 9
102000001419 Melatonin receptor Human genes 0.000 abstract description 7
108050009605 Melatonin receptor Proteins 0.000 abstract description 7
YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 28
DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 28
229960003987 melatonin Drugs 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 25
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
238000000034 method Methods 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 20
238000005481 NMR spectroscopy Methods 0.000 description 18
239000000047 product Substances 0.000 description 17
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
150000002431 hydrogen Chemical class 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000007787 solid Substances 0.000 description 13
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
208000035475 disorder Diseases 0.000 description 9
235000019439 ethyl acetate Nutrition 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000003921 oil Substances 0.000 description 8
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OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
239000004480 active ingredient Substances 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
238000001819 mass spectrum Methods 0.000 description 7
SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical class NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
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235000019341 magnesium sulphate Nutrition 0.000 description 4
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
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COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Cosmetics (AREA)
Hydrogenated Pyridines (AREA)
Indole Compounds (AREA)

CA002376949A 1999-06-30 2000-06-06 Heterocyclic aminopyrrolidine derivatives as melatonergic agents Expired - Lifetime CA2376949C (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US14189499P	1999-06-30	1999-06-30
US60/141,894		1999-06-30
PCT/US2000/015478 WO2001002392A1 (en)	1999-06-30	2000-06-06	Heterocyclic aminopyrrolidine derivatives as melatonergic agents

Publications (2)

Publication Number	Publication Date
CA2376949A1 CA2376949A1 (en)	2001-01-11
CA2376949C true CA2376949C (en)	2009-05-26

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CA002376949A Expired - Lifetime CA2376949C (en)	1999-06-30	2000-06-06	Heterocyclic aminopyrrolidine derivatives as melatonergic agents

Country Status (13)

Country	Link
US (1)	US6211225B1 (de)
EP (1)	EP1189900B1 (de)
JP (2)	JP4767463B2 (de)
AT (1)	ATE257834T1 (de)
AU (1)	AU763963B2 (de)
CA (1)	CA2376949C (de)
DE (1)	DE60007745T2 (de)
DK (1)	DK1189900T3 (de)
ES (1)	ES2213022T3 (de)
PE (1)	PE20010327A1 (de)
PT (1)	PT1189900E (de)
UY (1)	UY26226A1 (de)
WO (1)	WO2001002392A1 (de)

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BRPI0610037A2 (pt) *	2005-04-22	2010-05-25	Wyeth Corp	derivados de dihidrobenzofurano e uso dos mesmos
JP2008538571A (ja) *	2005-04-22	2008-10-30	ワイス	ジヒドロベンゾフラン誘導体およびその使用
JP2009538334A (ja) *	2006-05-22	2009-11-05	ヴァンダファーマシューティカルズインコーポレイテッド	抑うつ障害のための治療
CN101687810A (zh) *	2007-04-26	2010-03-31	武田药品工业株式会社	双环化合物及其药物用途
ES2331276B1 (es) *	2007-10-25	2010-10-21	Ferrer Internacional, S.A.	Compuestos de fenilpirrolidina.
EP2266975A1 (de) *	2009-06-15	2010-12-29	Ferrer Internacional, S.A.	1-(2-Alkyl-2,3-dihydrobenzofuran-4-yl)pyrrolidin-3-ylaminacyl-Verbindungen
CN104379135B (zh)	2012-01-26	2020-07-14	万达制药公司	昼夜节律紊乱的治疗
US11918557B2 (en)	2012-01-26	2024-03-05	Vanda Pharmaceuticals Inc.	Treatment of circadian rhythm disorders
ES2681593T3 (es)	2012-11-29	2018-09-14	Chemocentryx, Inc.	Antagonistas de CXCR7
BR112015014619A2 (pt)	2012-12-18	2017-07-11	Vanda Pharmaceuticals Inc	tratamento de transtornos do ritmo circadiano
US10376487B2 (en)	2013-11-12	2019-08-13	Vanda Pharmaceuticals Inc.	Method of treatment
US11090285B2 (en)	2013-11-12	2021-08-17	Vanda Pharmaceuticals Inc	Treatment of circadian rhythm disorders
BR102016024814A2 (pt)	2016-10-24	2018-05-08	Aché Laboratórios Farmacêuticos S.A.	composto, processo de obtenção do composto, composição farmacêutica, uso do composto e método de tratamento de desordens psiquiátricas e/ou distúrbios do sono
AU2019398198A1 (en)	2018-12-12	2021-07-08	Chemocentryx, Inc.	CXCR7 inhibitors for the treatment of cancer
CN109574970A (zh) *	2018-12-27	2019-04-05	上海毕得医药技术有限公司	一种5-溴苯并二氢吡喃的合成方法

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FR2680366B1 (fr)	1991-08-13	1995-01-20	Adir	Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
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FR2725985B1 (fr)	1994-10-21	1996-11-15	Adir	Nouveaux composes tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
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EP0901483B1 (de)	1996-05-14	2003-07-09	Glaxo Group Limited	Benzofurane und benzpyrane als chronobiologische mittel
CN1152679C (zh) *	1996-12-10	2004-06-09	布里斯托尔-迈尔斯斯奎布公司	苯并二氧杂环戊烯、苯并呋喃、二氢苯并呋喃和苯并二噁烷类化合物褪黑激素能药剂
FR2761358B1 (fr) *	1997-03-27	1999-05-07	Adir	Nouveaux composes de n-aryl piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

2000
- 2000-06-06 US US09/587,928 patent/US6211225B1/en not_active Expired - Lifetime
- 2000-06-06 ES ES00938160T patent/ES2213022T3/es not_active Expired - Lifetime
- 2000-06-06 DE DE60007745T patent/DE60007745T2/de not_active Expired - Lifetime
- 2000-06-06 EP EP00938160A patent/EP1189900B1/de not_active Expired - Lifetime
- 2000-06-06 AU AU53240/00A patent/AU763963B2/en not_active Expired
- 2000-06-06 WO PCT/US2000/015478 patent/WO2001002392A1/en active IP Right Grant
- 2000-06-06 JP JP2001507829A patent/JP4767463B2/ja not_active Expired - Lifetime
- 2000-06-06 CA CA002376949A patent/CA2376949C/en not_active Expired - Lifetime
- 2000-06-06 PT PT00938160T patent/PT1189900E/pt unknown
- 2000-06-06 AT AT00938160T patent/ATE257834T1/de active
- 2000-06-06 DK DK00938160T patent/DK1189900T3/da active
- 2000-06-28 UY UY26226A patent/UY26226A1/es not_active Application Discontinuation
- 2000-06-28 PE PE2000000652A patent/PE20010327A1/es not_active Application Discontinuation
2011
- 2011-04-07 JP JP2011085583A patent/JP5248647B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
AU763963B2 (en)	2003-08-07
DE60007745T2 (de)	2005-03-10
ES2213022T3 (es)	2004-08-16
EP1189900A4 (de)	2002-07-31
WO2001002392A1 (en)	2001-01-11
PT1189900E (pt)	2004-05-31
US6211225B1 (en)	2001-04-03
ATE257834T1 (de)	2004-01-15
DE60007745D1 (de)	2004-02-19
PE20010327A1 (es)	2001-06-10
JP4767463B2 (ja)	2011-09-07
DK1189900T3 (da)	2004-04-26
JP2003503492A (ja)	2003-01-28
AU5324000A (en)	2001-01-22
EP1189900A1 (de)	2002-03-27
JP2011137043A (ja)	2011-07-14
JP5248647B2 (ja)	2013-07-31
EP1189900B1 (de)	2004-01-14
UY26226A1 (es)	2001-01-31
CA2376949A1 (en)	2001-01-11

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